Experimental Animal Science

Comparison of the postoperative analgesic effects

of buprenorphine and piritramide following
experimental orthopaedic surgery in sheep
K. A. OTTO~, K. H. S. STEINER 1, F. ZAILSKAS 2, and B. WIPPERMANN2

~Departmentof Laboratory Animal Science, and

2Department of Orthopaedic Surgery, Medical School Hannover, Hannover, Germany

With 3 figures and 2 tables

Summary
• Introduction: Long-acting opioids may be needed for postoperative pain relief in sheep.
Reports on the analgesic efficacy of the partial ~ agonist buprenorphine, however, are controver-
sial. Therefore, the aim of this study was to compare the effects of buprenorphine with the g full
agonist piritramide on clinical pain following orthopaedic surgery in sheep.
• Material and methods: Postoperative analgesia of intramuscular buprenorphine (0.01 mg/kg)
and piritramide (0.57 mg/kg) were evaluated in a prospective, randomised and blinded study in
22 ewes submitted to an experimental tibia osteotomy. For evaluation of postoperative analgesia
the time from extubation to first attempt to stand, to standing, to first food/water uptake, to first
postoperative analgesic treatment, the number of animals treated per group, postoperative
behaviour and lameness scores were compared.
• Results: The distribution of behavioural scores in standing/walking animals was significantly
different (P = 0.018) between the two treatment groups. In the buprenorphine group behaviour
scores ranged more in the lower score range while higher scores were recorded in the piritramide
group. In both groups the same number of nine sheep required additional postoperative analgesic
treatment at almost identical time intervals. No significant differences existed for the other vari-
ables.
• Conclusion: Buprenorphine and piritramide provided effective analgesia following tibia
osteotomy in sheep with a slightly better quality in animals pre-treated with buprenorphine.

Key words: Buprenorphine, piritramide, postoperative analgesia, sheep

J. Exp. Anita. Sci. 2000; 41:133-143

Urban & Fischer Verlag
http://wwwurbanfischer'de/j °urnals/jeansc
0939-8600/00/41/03-133 $15.00/0
134 K.A. OTTOet al.

Introduction

The analgesic regimen suitable for postoperative pain relief in experimental animals
depends on the species, the surgical procedure and the aim of the study. In sheep sub-
jected to unilateral tibia osteotomy pronounced rear limb weakness associated with a high
risk of postoperative injury may be expected following epidural administration of local
anaesthetics (TRIM 1989, HENDRICKSONet al. 1996). Furthermore, treatment with o~2-ago-
nists may lead to rumenal atony, bloat and prolonged recovery (TRIM1987) and the use of
nonsteroidal antiinflammatory drugs (NSAIDs) may be contraindicated if evaluation of
inflammatory reactions at the surgical site is a major objective of the study. Therefore,
opioid analgesics may be the only choice for postoperative pain relief following rear limb
surgery in sheep.
Buprenorphine is a partial ~ opioid receptor agonist (DUMand HERZ 1981). Its anal-
gesic potency relative to morphine in rodents and human patients has been reported to
be in the range from 1 to 100 (BRYANTet al. 1983), 25 to 50 (JAFFEand MART~N 1985)
or 25 to 40 (CowAN et al. 1977, SORGE 1993). Buprenorphine has been characterised as
a long-lasting opioid analgesic with a duration of action of approximately six to 12
hours (DONADONIand ROLLY 1987, JENKINS 1987, JAGE and JURNA 1993, SORGE 1993,
WALDVOGELet al. 1996) and with minimal cardiovascular and respiratory side effects
(TAYLORand HOVLTON 1984, WATERMANet al. 1991, STEPmN et al. 1995). Its use for
postoperative analgesia in orthopaedic surgeries including the hip, thigh, knee, and
lower leg has been reported in human patients and dogs (LANZ et al. 1984, TAYLORand
HOULTON 1984, BILSBACK et al. 1985, DONADONI and ROLLY 1987). Reports on the
analgesic efficacy of buprenorphine in animals, however, are controversial. While
effective postoperative pain relief has been reported for buprenorphine in clinical pain
following orthopaedic surgeries and thoracotomies in dogs (TAYLOR et al. 1984,
CONZEMIUS et al. 1994), experimental studies in sheep revealed thermal but no
mechanical antinociception over a wide dose range of buprenorphine (NOLANet al.
1987, WATERMANet al. 1991, LIVINGSTONet al. 1992, WELSH and NOLAN 1995, GRANT
et al. 1996). The dose-dependent variability in analgesic potency of buprenorphine in
rodents has been related to the bell-shaped dose response curve indicating a ceiling to
analgesic effect (COWAN et al. 1997, BRYANT et al. 1983, DUM and HERTZ 1981,
MCQUAY 1991).
Piritramide is a synthetic full ~ opioid receptor agonist (KIETZMANNet al. 1996) with
properties similar to buprenorphine. Piritramide has a duration of action of approximately
six to eight hours and provides analgesia without clinically relevant haemodynamic and
respiratory depression (SoRGE 1993, WALDVOOELet al. 1996, KIETZMANNet al. 1997). Its
potency in human patients is approximately 0.7 times that of morphine (SORGE 1993,
KIETZMANN et al. 1996). Piritramide has been used for more than 30 years in parts of
Europe as the analgesic of choice for the management of postoperative pain (KUMARand
ROWBOTHAM 1999). The perioperative use of piritramide has been reported in a few ani-
mal studies including pigs (KOPPER 1984) and dogs (KETTLERet al. 1971, SPIEGELet al.
1986, OTTOet al. 1997).
 Comparison of the postoperative analgesic effects of buprenorphine and piritramide 135

Bnprenorphine and piritramide may be suitable analgesics for postoperative pain relief
after orthopaedic rear limb surgery in sheep, based on their long duration of action and
the low potential for cardiorespiratory side effects. To our knowledge the postoperative
analgesic effects of both opioids have yet not been compared for clinical pain in sheep.
Therefore, the aim of this study was to compare postoperative responses in sheep treated
with equipotent doses of either buprenorphine or piritramide.

Material and methods

Animals
In a prospective, randomised and blinded study postoperative analgesia was evaluated in 22
ewes (Deutsches Schwarzk6pfiges Fleischschaf). The study was approved by the University and by
the Animal Care and Use Committee at the local district government (Ts-Nr.: 604i-42502-96A682
and 604i-42502-97/968). The sheep, approximately two to four years old and weighing between 57
and 98 kg, were systemically healthy based on physical examination. Food but not water was with-
held for 24 hours before surgery. All sheep were submitted to an experimental tibia osteotomy at
the left rear limb.

Treatment Groups
The sheep were randomly assigned into one of two preoperative treatment groups:
BUP (n = 11): Buprenorphine (Temgesic; Reckitt & Colman Products Ltd., U.K.) at 0.01 mg/kg
body weight (bwt) intramuscularly (IM).
PIR (n = 11): Pifitramide (Dipidolor; Janssen GmbH, Neuss, Germany) at 0.57 mg/kg bwt IM.

Buprenorphine or piritramide were administered into the quadriceps and semitendinous muscles
shortly after induction of anaesthesia. Based on the type of the surgical procedure a control group of
sheep given saline or no analgesic was considered unjustifiable on humanitarian grounds. The cal-
culation of equipotent doses of buprenorphine and piritramide was based on previously published
data on the analgesic potency of buprenorphine and piritramide relative to morphine in rodents and
human patients. For buprenorphine we chose a relative potency of 40 (CoWAN et al. 1977, SOR~E
1993) and for piritramide of 0.7 (KIETZMaNNet al. 1996), respectively.

Anaesthetic Protocol
Anaesthesia was induced with sodium pentobarbitone (Nembutal; Sanofi Ceva GmbH, Dfissel-
doff, Germany; Vertrieb: Wirtschaftsgenossenschaft deutscher Tieriirzte e. G,, Garbsen, Germany)
(Tab. 1) via a 14-gauge jugular venous catheter (Cavafix; B. Braun Melsungen AG, Melsungen,
Germany). The sheep were orotracheally intubated with a cuffed endotracheal tube, a stomach tube
was inserted into the rumen and dexpanthenol eye ointment was applied (Bepanthen Roche, Hoff-
mann La Roche AG, Grenzach-Whylen, Germany). In the operating room the animals were con-
nected to a semi-closed rebreathing circuit (Sully 808 V-D, Dr~igerwerk AG, Li~beck, Germany) and
anaesthesia was maintained with 1.5% to 2% halothane (vaporiser setting) (Vapor 19.3, DrSgerwerk
AG, Lfibeck, Germany) in oxygen (2 L/rain). Ventilation was controlled (Ventilog 3, Dr~igerwerk
AG, Ltibeck, Germany) using intermittent positive pressure ventilation (IPPV). Lactated Ringers
solution (B. Braun Melsungen AG, Melsungen, Germany) was administered for maintenance at
5 ml/kg/hr. For recovery from anaesthesia the sheep were placed in a box padded with straw. The
sheep were kept in sternal recumbency. The endotracheal tube was removed when the animals were
able to swallow and capable of supporting themselves in sternal recumbency (GRAY 1986).
136 K.A. OTTO et al.

Surgical Procedures
After aseptic preparation of the surgical site the left tibia was osteotomised and a bone fragment
of a length of 3 cm was removed. Thereafter, the tibia was stabilised by a medullary nail osteo-
synthesis, the bone defect was filled with bone replacement substance and the wound was closed.

Evaluation of postoperative analgesia

For evaluation of postoperative analgesia the following variables were used: (1) time from extu-
bation to first attempt to stand, (2) time to standing, (3) time to first food/water uptake, (4) time to
postoperative analgesic treatment with buprenorphine (0.6 mg IM) and (5) the number of animals
per group treated within the first 12 hours following extubation. In addition, individual behaviour
(6) and degree of lameness (7) were scored (see Appendix) at 10, 20, 30, 60, 90, 120, 150, 180, 240,
300, 360, 480, 600 and 720 minutes after extubation. Individual behaviour in resting/recumbent
sheep and standing/walking sheep, respectively, was evaluated separately. Prior to the study it was
decided to treat the sheep with additional analgesic (buprenorphine; 0.6 mg IM) whenever lameness
was scored with 3.5 or 4 at two subsequent observations regardless of the behavioural score. These
sheep were excluded from further scoring. The observing veterinarian was blinded to the treatment
protocol.

Data analysis
A Hest for independent samples (SigmaStat ® Version 2.0, SPSS Science Software GmbH,
40688 Erkrath, Germany) was used for comparison of metric data between the two treatment
groups. Chi-Square (?(2) analysis was used for comparison of scored data between the treatment
groups. Significance level was set at P < 0.05. Data are represented as mean ± standard deviation
(sd) (Table 1 and 2) and as frequency distribution (Figure 1 to 3).

Table 1. Mean (sd) anaesthestic data in 21 sheep submitted to unilateral tibia osteotomy.

Variable Buprenorphine Piritramide P

(n = l l ) (n = 10)

Body weight (kg) 79.4 ± 12.6 84.3 + 12.3 0.377

Pentobarbitone (mg/kg IV) 21.0 _+2.72 20.9 _+ 1.87 0.950
Duration of anesthesia (rain) 149.1 +__26.4 148.5 ± 24.8 0.958
Duration of surgery (min) 75.9 ± 19.5 70.0 ± 15.8 0.457

Table 2. Mean (sd) durations during postoperative recovery from unilateral tibia osteotomy in 21
sheep.

Variable Buprenorphine Piritramide P

(n = 11) (n = 10)

Time to 1st attempt to stand (rain) 70.0 :e 65.2 51.6 + 49.7 0.480
Time to standing (rain) 152.7 +_94.2 153.0 ± 57.1 0.994
Time to 1st food/water uptake (rain) 43.6 ± 21.7 55.0 + 80.4 0.656
Time to 1st postoperative analgesic treatment (rain) 310.0 ± 143.9 313.0 ± 148.6 0.962
 Comparison of the postoperative analgesic effects of buprenorphine and piritramide 137

Results

In one sheep of the piritramide group, internal stabilisation of the tibia fragments
resulted in a diaphyseal fracture requiring an additional cerclage for fixation. This sheep
was treated with additional buprenorphine in the early recovery period and was excluded
from the study resulting in a decreased number of sheep (n = 10) in the piritramide group.
Differences between the two treatment groups in body weight, dose of pentobarbitone,
duration of anaesthesia, and duration of surgery were not statistically significant (Table
1).
The mean time from extubation to standing (BUP: 152.7 min, PIR: 153.0 rain) and
from extubation to first postoperative analgesic treatment (BUP: 310.0 rain and PIR:
313.0 min) was almost identical for the two treatment groups (Table 2). Furthermore, in
both groups the same number of nine sheep received additional analgesic treatment
within the first 12 hours following extubation. In sheep treated with buprenorphine mean
time from extubation to first attempt to stand was longer (BUP: 70 min, PIR: 51.6 min)
and from extubation to first food/water uptake was shorter (BUP: 43.6, PIR: 55 rain)
compared with those treated with piritramide. Differences, however, were not statistically
significant (Table 2).
The behavioural scores for recumbent and standing/walking sheep, respectively, have
been represented as percentage of total number of observations (Figure 1 and 2). The max-
imum possible behavioural score of 7 was not achieved in any sheep. The highest score of
4 was graded only once in one sheep treated with piritramide while in the majority of
sheep of both treatment groups behavioural scores ranged between 0 and 2. No statistically
significant differences in the distribution of behavioural scores existed between recumbent
sheep of both groups (P = 0.245) (Figure 1). In standing/walking sheep, however, the dis-

s0

45

40

.£ 35

30
O 25

o 20
I--

10

0
0 0,5 1 1,5 2 2,5 3
Behavioural Score in Recumbent Sheep

Fig. 1. Frequency distribution of postoperative behaviour scores in recumbent sheep (% of total

observations) between extubation and 1st postoperative analgesic treatment following unilateral
tibia osteotomy.
 138 K.A. OTTOet al.

60-

50"

o 40 -

0 30-

0
I--
"8 20

10-

O- i!ili' I I I I I I I
0 0=5 1 1,5 2 2,5 3 3,5 4
Behavioural Score in Standing/Walking Sheep

Fig. 2. Frequency distribution of postoperative behaviour scores in standing/walking sheep (% of

total observations) between extubation and 1st postoperative analgesic treatment following unilat-
eral tibia osteotomy.

3O

25
o
~ii~i!!!iiiili!

20 ....

1
0 :~!ili!iiiii~il
15 i ~iii!iiiiii
o
I- i~ii!i%il
"10

!i!!i'iiiiiii!
'
5
~i ~~!~iiii~~i~
!!izi!iii!i!i

0 '
2 2,5 3 3,5 4
Lameness Score

Fig. 3. Frequency distribution of postoperative lameness scores in sheep (% of total observations)

between extubation and 1st postoperative analgesic treatment following unilateral tibia osteotomy.

tribution of behavioural scores between the two treatment groups was significantly differ-
ent (P = 0.018) (Figure 2). In sheep pre-treated with buprenorphine the incidence of lower
behavioural scores was more pronounced compared with the piritramide group.
The lameness grading system revealed a higher incidence of lower scores (2 to 3) in
sheep treated with buprenorphine while lameness was graded more frequently with
higher scores in the piritramide group (Figure 3). Differences in lameness scores between
the two treatment groups, however, were not statistically significant (P = 0.292).
 Comparison of the postoperative analgesic effects of buprenorphine and piritramide 139

Discussion

The partial ~t agonist buprenorphine may provide efl'ective postoperative analgesia in

clinical pain following orthopaedic surgeries and thoracotomies in dogs (TAYLORet al.
1984, CONZEMIUSet al. 1994) and has been also suggested for long-lasting analgesia up to
12 hours in sheep (JENKINS 1987). However, there are conflicting reports on the analgesic
efficacy of buprenorphine in sheep (NoI, AN et al. 1987, WATERMANet al. 1991, LIV-
iNGSTON et al. 1992, WELSH and NOLAN 1995, GRANT and others 1996). Intravenous
administration of buprenorphine at 1.5, 6 and 12 ~ag/kg in experimental pain models pro-
duced dose-dependent significant analgesia against a thermal stimulus but failed to pro-
duce mechanical antinociception (WATE~AN et al. 1991). On the other hand ~t agonists
such as pethidine and fentanyl produced effective thermal and mechanical antinocicep-
tion in sheep (LIWNGSTONet al. 1992). Therefore, the aim of the study was to compare
postoperative analgesia following administration of equipotent doses of two long-lasting
opioids, the partial ~t agonist buprenorphine and the p agonist piritramide.
For comparison of the postoperative analgesic effects of both opioid analgesics the
time to first attempt to stand, time to standing, time to food/water uptake (HENDRICKSON
et al. 1996), time to first postoperative analgesic treatment and the number of animals
treated within the first 12 hours (LANZet al. 1984, DONADONIand ROLL¥ 1987, MORL~ON
et al. 1999), a behaviour score (PABLO 1993, HENDR~C~:SONet al. 1996) and a lameness
score (VAsSEURet al. 1995) were employed.
Data analysis revealed no statistically significant differences between the two treatment
groups for most variables except for the behaviour score in standing/walking sheep sug-
gesting that buprenorphine provided effective postoperative analgesia following unilateral
tibia osteotomy in sheep. This assumption is firstly based on the results of the behaviour
grading system. The maximum achievable total behavioural score was 7. The highest score
of 4 was graded only once in one sheep pre-treated with piritramide while in nine sheep
(81.8%) pre-treated with buprenorphine and in six sheep (60%) pre-treated with pir-
itramide, respectively, total behavioural scores at the distinct observation time points
ranged between 0 and 2. Secondly, additional postoperative administration of 0.6 mg
buprenorphine IM clinically improved general behaviour and degree of lameness in all
sheep including the one excluded from the study because of an intraoperative tibia fracture.
Thirdly, the average duration from extubation to eating ranged between 43.6 (buprenor-
phine) and 55.5 (piritramide) minutes, respectively, and thus was close to the average time
to eating of approximately 48 minutes in goats treated effectively with morphine (HEN-
DRICKSONet al. 1996). The much longer time to standing recorded in our study compared to
data reported by HENDRICKSONand coworkers (1996) may have been caused by the differ-
ent type of surgeries (tibia osteotomy versus right paramedian abomasopexy). Finally, pre-
operative injection of either buprenorphine or piritramide was performed shortly after
induction of anaesthesia. Taking the mean anaesthesia time and mean time from extubafion
to first postoperative analgesic treatment into account, then the sheep of both groups
received additional buprenorphine approximately seven to eight hours after preoperative
treatment. This finding confirms data on the duration of analgesia for buprenorphine and
140 K.A. OTTOet al.

piritramide in the range from six to 12 hours (DONADONIand ROLLY 1987, JENKINS 1987,
JA6E and JURNA 1993, SORGE 1993, WALDVOGELand others 1996) and from six to eight
hours (SORGE 1993, WALDVO6ELet al. 1996, KIETZMANNet al. 1997), respectively.
Differences in the efficacy between different treatment modalities may appear only
when pain is assessed during function such as mobilisation (KEHLET 1994). Therefore, we
scored overall behaviour in recumbent and standing/walking sheep separately. Analysis
of data obtained from standing/walking sheep revealed a statistically significant differ-
ence in behaviour scores between the two treatment groups. The higher incidence of low
behaviour scores in the buprenorphine group and the higher incidence of high behaviour
scores in the piritramide group may suggest a more effective analgesia upon mobilisation
following pre-treatment with buprenorphine.
The study design used, however, does not allow more detailed information on the qual-
ity of analgesia of either drugs. Because of the limited number of sheep that underwent
the same surgery performed by the same surgeon, we compared only one dose of each
drug. Using multiple doses of each analgesic may have led to more pronounced differ-
ences between the treatment groups not obvious when using a single dose comparison
study. In addition, we did neither include a positive control group treated with a local
anaesthetic (HENDRICKSONet al. 1996) nor a negative control with saline for the reasons
mentioned before. This might also have provided more detailed information on the anal-
gesic efficacy of buprenorphine and piritramide. In a previous experimental study in
sheep (GRANT et al. 1996) treated either with xylazine, buprenorphine, methadone or flu-
nixin meglumine, xylazine was found to be the only effective analgesic. The benefits to
expect from xylazine in the present study, however, may have been limited. Additional
postoperative treatment with xylazine in two sheep submitted to the same type of surgery
in an earlier study did not improve clinical analgesia.
All data used for postoperative evaluation were obtained by observation. The sheep
used in the present study were untrained herd animals not used to personal contact. In
order to avoid escape behaviour associated with a high risk of postoperative injury such as
fracture of th e surgical limb we decided not to measure postoperative haemodynamic or
endocrine responses to treatment. Whether these measurements would have provided
more detailed information on the analgesic efficacy of buprenorphine and piritramide can-
not be answered. A previous study on the determination of severity of postoperative pain
in dogs revealed that subjective measures of pain including scores for visual analogue and
numerical rating scales did not correlate or correlated poorly with objective measures such
as heart rate, respiratory rate, blood pressure and results of a pain threshold test
(CoNzEN~US et al. 1997). Therefore, the variables chosen in this study may have been ade-
quate for evaluation of postoperative analgesia. A comparison of a numerical rating scale
(NRS), as it has been used in this study, and a visual analogue scale (VAS) for subjective
assessment of lameness, however, revealed that the VAS is inherently more sensitive
(WELS~ et al. 1993). Therefore, using a VAS for assessment of postoperative behaviour
and lameness instead of a NRS may have been advantageous in the present study.
The majority of sheep were graded with the lowest behavioural scores of 0 to 2. How-
ever, all but three sheep received additional analgesic treatment within the first 12 hours
 Comparison of the postoperative analgesic effects of buprenorphine and piritramide 141

postoperatively based on the high lameness scores in order to assure the most possible
pain relief. Referring to the type of surgery we would not expect lamefree sheep regard-
less of type and dose of drug or technique used for postoperative analgesia. Therefore, it
may be questioned whether a lameness score or and behaviour score should be used as
physiological end-point in the assessment of adequate pain relief following invasive
orthopaedic procedures in sheep.
In conclusion, based on the study design our data suggest that pre-treatment with either
buprenorphine (0.01 mg/kg IM) or piritramide (0.57 mg/kg) provided effective postoper-
ative analgesia following tibia osteotomy with a slightly better quality in sheep pre-
treated with buprenorphine. Further studies, however, will be needed for more detailed
information on the quality of analgesia of both drugs in sheep.

A p p e n d i x 1. Behavioural Grading System.

Category Clinical signs Score

Vocalisation none 0
teeth grinding (occasionally) l
teeth grinding (frequently); bleets and grunting before expiration 2
Activity asleep; lying down or standing quietly 0
frequent position changes; frequent attempts to get up 1
restlessness; moving around; thrashing 2
Food and water uptake eating, drinking 0
no food or water uptake 1
Facial expression interested in the surrounding; looking for straw, hay or water 0
looking depressed, looking at the wound 1
Respiratory rate 20 breaths per minute (normal)* 0
25 to 50% above normal 0.5
more than 50% above normal 1

*A rate of 20 breaths per minute (GREEN 1979) was taken as baseline value instead of using indi-
vidual preoperative breathing rates in order to compensate for increases in respiratory rate due to
excitement.

A p p e n d i x 2. Lameness grading system.

Category Clinical signs Score

Lameness Stands and walks normally 0

Stands normally; slight lameness when walking 1
Stands normally; severe lameness when walking 2
Abnormal posture when standing; severe lameness when walking 3
Does not bear weight on the surgical limb at rest or when walking 4

Intermediate scores (e.g. 2.5) were used when the degree of lameness could not be clearly defined
at one time point.
142 K.A. OTTO et al.

References
BILSBACK,P., G. ROLLY, and O. TAMPUBOLON. 1985. Efficacy of the extradural administration of
lofentanil, buprenorphine or saline in the management of postoperative pain. A double-blind
study. Br. J. Anaesth. 57:943-948
BRYANT, R. M., J. E. OLLEY, and M. B. TYERS. 1983. Antinociceptive actions of morphine and
buprenorphine given intrathecally in the conscious rat. Br. J. Pharmac. 78:659-663
CONZEMIUS,M. G., D. J. BROCKMAN,L. G. KING,and S. Z. PERKOWSKI. 1994. Analgesia in dogs
after intercostal thoracotomy: A clinical trial comparing intravenous buprenorphine and inter-
pleural bupivacaine. Vet. Surg. 23:291-298
CONZEM1US,M. G., C. M. HILL, J. L. SAMMARCO,and S. Z,. PERKOWSKI.1997. Correlation between
subjective and objective measures used to determine severity of postoperative pain in dogs. J.
Am. Vet. Med. Assoc. 210:1619-1622
COWAN, A., J. W. LEWIS, and I. R. MACFARLANE. 1977. Agonist and antagonist properties of
buprenorphine, a new antinociceptive agent. Br. J. Pharmac. 60:537-545
DONADONI, R., and G. ROLLY. 1987. Epidural sufentanil versus intramuscular buprenorphine for
postoperative analgesia. A double-blind comparative trial. Anaesthesia 42:1171-1175
DUM, J. E., and A. HERZ. 1981. In vivo receptor binding of the opiate partial agonist, buprenor-
phine, correlated with its agonistic actions. Br. J. Pharmac. 74:627-633
GRANT, C., R. N. UPTON, and T. R. KUCHEL. 1996. Efficacy of intra-muscular analgesics for acute
pain in sheep. Australian Veterinary Journal 73:129-132
GRAY, P. R. 1986. Anesthesia in goats and sheep. Part II. General anesthesia. Comp. Contin. Educ.
Pract. Vet. 8:127-135
GREEN, C. J. 1979. Animal Anaesthesia. Laboratory Animal Handbooks 8, p 185. London, Labora-
tory Animals Ltd
HENDRICKSON,D. A., K. T. KRUSE-ELLIOT,and R. V. BROADSTONE.1996. A comparison of epidural
saline, morphine, and bupivacaine for pain relief after abdominal surgery in goats. Vet. Surg. 25:
83-87
JAFFE,J. H., and W. R. MARTIN. 1985. Opioid analgesics and antagonists. In GOODMANGILMAN,A.,
L. S. GOODMAN,T. W. RALL, and F. MURAD, eds, The Pharmacological Basis of Therapeutics
(7th edn), 491-531, Macmillan, New York
JAGE, J. and I. JURNA. 1993. Opioidanalgetika. In ZENZ, M., und K. JURNA, Hrsg., Lehrbuch der
Schmerztherapie. Grundlagen, Theorie und Praxis fiir Aus- und Weiterbildung, 173-153, Wis-
senschaftliche Verlagsgesellschaft mbH, Stuttgart
JENKINS, W. L. 1987. Pharmacologic aspects of analgesic drugs in animals: An overview. J. Am.
Vet. Med. Assoc. 191:1231-1240
KENLET, H. 1994. Postoperative pain r e l i e f - what is the issue. Editorial. Br. J. Anaesth. 72:
375-378
KETTLER,D., U. BRAUN,L. A. COTT, H. W. WEISS, I. HENSEL,J. MARTEL,K. PASCHEN,und H. J.
BRETSCnNEIDER. 1971. Kombination yon Piritramid und N20 - ein neues Narkoseverfahren. Teil
I: Tierexperimentelle Untersuchungen. Z. prakt. AnSsth. 5:329-339
KIETZMANN,D., I. BRIEDE,T. BOUOmLON,U. GUNDERT-REMY,and D. KEYrLER. 1996. Pharmacoki-
netics of piritramide after an intravenous bolus in surgical patients. Acta Anaesthesiol. Scand.
40:898-903
KIETZMANN,D., T. BOUILLON,C. HAMM, K. SCHWABE,H. SCHENK,U. GUNDERT-REMY,and D.
KETTLER. 1997. Pharmacodynamic modelling of the analgesic effects of piritramide in postoper-
ative patients. Acta Anaesthesiol. Scand. 41:888-894
KOPPER, W. 1984. Schmerzausschaltung in der experimentellen Chirurgie bei Hund, Katze,
Schwein, Schaf, 85-87, Verlag Parey, Berlin
KUMAR,N., and D. J. ROWBOTHAM.1999. Piritramide. Editorial II. Br. J. Anaesth. 82:3-5
LANZ, E., G. SIMKO,D. THEISS,and M. H. GLOCKE. 1984. Epidural buprenorphine - A double-blind
study of postoperative analgesia and side effects. Anesth. Analg. 63:593-598
 Comparison of the postoperative analgesic effects of buprenorphine and piritramide 143

LIVINGSTON,A., A. E. WATERMAN,A. NOLAN,and A. AMIN. 1992. Comparison of the thermal and

mechanical antinociceptive actions of opioids and (x2-adrenoceptor agonists in sheep. In SHORT,
C. E., and A. VANPOZNAK,eds. Animal Pain, 372-377, Churchill Livingstone, New York
McQUAY, H. J. 1991. Opioid clinical pharmacology and routes of administration. British Medical
Bulletin 47:703-717
MORLION, B., E. EBNER, A. WEBER, W. FINKE,and C. PUCHSTEIN. 1999. Influence of bolus size on
efficacy of postoperative patient-controlled analgesia with piritramide. Br. J. Anaesth. 82:52-55
NOLAN, A., A. LIVINGSTON,and A, E. WATERMAN.1987. Investigation of the antinociceptive activ-
ity of buprenorphine in sheep. Br. J. Pharmac. 92:527-533
OTTO, K. A., B. P. WEBER, M. JACOBI,and H.-J. HEDR~CH. 1997. Retrospective evaluation of car-
diovascular and acid-base variables during long-term balanced anesthesia for experimental
surgery in dogs. Lab. Anim. Sci. 47:624-631
PABLO, L. S. 1993. Epidural morphine in goats after hindlimb orthopedic surgery. Vet. Surg. 22:
307-310
SOROE, J. 1993. Medikament6se Schmerztherapie. In ZENZ, M. und I. JURNA, Hrsg., Lehrbuch der
Schmerztherapie. Grundlagen, Theorie und Praxis ftir Aus- und Weiterbildung, 269-280, Wis-
senschaftliche Verlagsgesellschaft mbH, Stuttgart
SPIEGEL, H. U., M. BERGERMANN, J. HAUSS, M. WENDT, und K. SCHONLEBEN. 1986. Die
hochdosierte Piritramid-Basisanaestbesie in der experimentellen Anaesthesie und Chirurgie.
Anaesthesist 35:36-42
STEPIEN, R. L., J. D. BONAGURA,R. M. BEDNARSK~,and W. W. MUIR. 1995. Cardiorespiratory
effects of acepromazine maleate and buprenorphine hydrochloride in clinically normal dogs.
Am. J. Vet. Res. 56:78-84
TAYLOR, P. M., and J. E. F. HOULTON. 1984. Post-operative analgesia in the dog: A comparison of
morphine, buprenorphine and pentazocine. J. Small Anita. Pract. 25:437-451
TRIM, C. M. 1987. Special anesthesia considerations in the ruminant. In SHORT, C. E., ed., Princi-
ples & Practice of Veterinary Anesthesia, 285-300, Williams & Wilkins, Baltimore
TRIM, C. M. 1989. Epidural analgesia with 0.75% bupivacaine for laparotomy in goats. J. Am. Vet.
Med. Assoc. 194:1292-1296
VASSEUR,P. B., A. L. JOHNSON,S. C. BUDSBERG,J. D. LINCOLN,J. P. TOOMBS,J. G. WHITEHAIR,and
E. L. LENTZ. 1995. Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-
inflammatory drug, in the treatment of osteoarthritis in dogs. J. Am. Vet. Med. Assoc. 206:
807-811
WALDVOGEL, H. H., E. BEUBLER, and O. WILDER-SMiTH. 1996. Wirkstoffprofile zentraler Anal-
getika und Antinozizeptiva. In WALDVOGEL,U. H., Hrsg., Analgetika, Antinozizeptiva, Adju-
vanzien. Handbuch far die Schmerzpraxis, 343-616, Springer-Verlag, Berlin
WATERMAN,A. E., A. LIVINGSTON,and A. AMIN. 1991. Further studies in the antinociceptive activ-
ity and respiratory effects of buprenorphine in sheep. J. Vet. Pharmacol. Therap. 14:230-234
WELSH, E. M., G. GETTINBY,and A. M. NOLAN. 1993. Comparison of a visual analogue scale and a
numerical rating scale for assessment of lameness, using sheep as a model. Am. J. Vet. Res. 54:
976-983
WELSH, E. M., and A. M. NOLAN. 1995. The effects of abdominal surgery on thresholds to thermal
and mechanical stimulation in sheep. Pain 60: 159-166.

Corresponding author: K. A. OTTO, Department of Laboratory Animal Science, Medical School

Hannover, Carl-Neuberg-Str. l, D - 30625 Hannover, Germany